期刊
EMBO REPORTS
卷 12, 期 5, 页码 463-469出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/embor.2011.43
关键词
isocitrate dehydrogenase; 2-hydroxyglutarate; 2-oxoglutarate; oxygenases; hypoxia-inducible factor
资金
- Wellcome Trust
- Biotechnology and Biological Sciences Research Council, UK
- German Academic Exchange Service
- Malaysian Government
- Univerisiti Sains Malaysia
Mutations in isocitrate dehydrogenases (IDHs) have a gain-of- function effect leading to R(-)-2-hydroxyglutarate (R-2HG) accumulation. By using biochemical, structural and cellular assays, we show that either or both R-and S-2HG inhibit 2-oxoglutarate (2OG)-dependent oxygenases with varying potencies. Half-maximal inhibitory concentration (IC(50)) values for the R-form of 2HG varied from approximately 25 mu M for the histone N(epsilon)-lysine demethylase JMJD2A to more than 5mM for the hypoxia-inducible factor (HIF) prolyl hydroxylase. The results indicate that candidate oncogenic pathways in IDH-associated malignancy should include those that are regulated by other 2OG oxygenases than HIF hydroxylases, in particular those involving the regulation of histone methylation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据